Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus, thought to be caused by food allergy, and characterized by the presence of eosinophils within the esophageal mucosa. Even though it is a relatively new disease, EoE is now recognized to be common in both adult and pediatric populations and rapidly rising in incidence. Patients with EoE can experience a variety of upper GI symptoms, ranging from dysphagia to food impaction. Experts fear that if left untreated, EoE may lead to esophageal fibrosis and stricture formation. It is therefore currently recommended that this disease be treated until the symptoms and the eosinophilic infiltrate have resolved. EoE therapy options include corticosteroids and aggressive dietary restriction followed by gradual food reintroduction. While both treatments are effective, EoE returns following cessation of corticosteroids and numerous attempts at food reintroduction are needed to arrive at a diet that provides a good quality of life. As a result, management of EoE patients involves frequent follow up to monitor the patient's clinical and histopathologic response to changes in steroid dosing and/or diet. This strategy is arduous for patients and their families, and costly, as multiple endoscopy sessions must be conducted over time to procure esophageal biopsies and monitor eosinophil counts. We have developed a new technology called spectrally-encoded confocal microscopy (SECM), that is capable of being incorporated into a small-diameter probe and can rapidly obtain depth-resolved microscopic image data over large epithelial areas in vivo. Originally developed to evaluate dysplasia and cancer of the esophagus, we have recently discovered that this imaging modality can also see esophageal eosinophils with a high degree of contrast. Much of the inconvenience and nearly half of the cost of endoscopy is a consequence of patient sedation that is required to perform the endoscopic procedure. In this proposal we will advance the SECM technology so that it can be used to monitor esophageal eosinophils without requiring sedation, endoscopy, or excisional biopsy. We will accomplish this task by developing small, flexible transnasal SECM probe that can be routinely inserted into the esophagus in the outpatient setting. In conjunction with a new high-speed SECM system, this device will automatically image a large portion of the esophagus and count eosinophils. Once the device has been constructed, validation studies will be conducted to demonstrate that the accuracy of this device is comparable to that of endoscopic biopsy. The end product of this research will be an esophageal eosinophil monitoring tool that is less expensive and far better tolerated than the current standard of care. Beyond its immediate clinical impact, this technology can also be used in future investigational studies to expand our knowledge of EoE and other diseases such as asthma that are characterized by tissue eosinophilia. PUBLIC HEALTH RELEVANCE: Eosinophilic esophagitis is an emerging disease caused by food allergy and characterized by the infiltration of eosinophils within the esophagus. This proposal will develop and clinically validate a novel imaging method for monitoring esophageal eosinophils that is less costly and better tolerated than endoscopic biopsy, the current diagnostic standard of care.